Natural cell-mediated cytotoxicity against tumor cells may be one of the host defense mechanisms against cancer. Studies on natural killer cells (NK) of unimmunized mice show that in vitro NK reactivity against certain tumors parallels the in vivo resistance to the same tumors. I propose to: 1) study the genetic controls which determine the expression of NK activity in mice and 2) further characterize the effector cell which mediates NK activity. Specifically I will: 1) determine if genetic controls operate at strain- and/or target cell-levels; 2) analyze linkage between levels of NK reactivity with known genetic markers; 3) attempt to establish congenic mouse strains differing only in levels of NK reactivity; and 4) characterize and enrich for NK effector cells by biophysical techniques as well as by serological means using sera containing anti-NK specificities. The long-range goals are to determine if reagents which augment in vitro NK activity correlate with increased tumor resistance in vivo and to study the differentiation stages of the NK cell.